With the advent of highly active antiretroviral therapy, human immunodeficiency virus (HIV) infection has become a chronic disease frequently co-existing with chronic use of prescribed, experimental and illicit drugs, including that of cannabinoids. Tetrahydrocannabinol (A9-THC) the most potent psychoactive constituent of marijuana, exerts multiple systemic effects in addition to the well recognized neurobehavioral disruption, including marked alterations in immune function. Understanding the impact of A9-THC, on immune and neurobehavioral function in HIV infection is particularly important, as its use has been approved as adjuvant therapy for appetite stimulation in acquired immunodeficiency syndrome (AIDS) patients. However, the metabolic impact of its chronic use as well as the immune and neurobehavioral consequences in the HIV-infected individual have not been carefully examined. Our working hypothesis to be tested in this non-human primate model of SIV infection is that chronic A9-THC treatment will: a) increase caloric intake and prevent loss of fat mass without improving retention of lean body mass, b) adversely affect immune function, increasing plasma and cerebrospinal fluid viral load and c) unmask the AIDS-related neurobehavioral deficits. The specific aims of the studies are to determine the impact of chronic A9-THC administration on a) caloric intake, body weight and composition and the balance of skeletal muscle protein synthesis and breakdown, the main determinants of lean body mass; b) plasma and cerebrospinal fluid viral load, immune phenotype and markers of immune competence and c) the occurrence of neurobehavioral dysfunction and neuropathological indices of inflammation and axonal damage in SIV-infected rhesus macaques. Overall, the proposed studies will examine the impact of chronic A9-THC administration on three key aspects; body composition, immune function and cognitive performance throughout the course of SIV infection until the terminal AIDS stage in a controlled experimental setting. Findings from these studies will provide objective scientific evidence on the effects of chronic marijuana abuse and will provide critical information about the potential health consequences of cannabinoid use in individuals with HIV infection/AIDS.